The most well characterized function of C1q, a subunit of the first component of complement, C1, is its recognition of foreign material or immune complexes and subsequent initiation of the classical complement pathway ultimately leading to the lysis neutralization or clearance of the potentially detrimental agent. C1q also plays a role in the inhibition of precipitation of immune complexes. Our previous work has demonstrated that C1q binds to specific surface receptors on human peripheral blood B cells, monocytes and polymorphonuclear leukocytes. The current research program is directed toward the elucidation of the physiologic role of this interaction of C1q with its cellular receptors and with other molecules of potentially physiologic relevance. Thus, the program has three main areas of focus. First, investigations of both the regulation of expression of the cellular receptor and its function have been initiated. We have determined both the number of C1q binding sites per cell and the affinity of C1q for its receptor after incubation of neutrophils and monocytes with the activation peptide f-met-leu-phe or with phorbol dibutrate (PDBu). Similarly, we have begun to investigate B cells at various stages of activation and differentiation by extending our studies to B cells derived from tonsils and spleen and further separated into subsets defined by size (i.e., the small, non-proliferating cells and the large, activated cells). Parallel functional studies suggest that C1q may affect the extent of differentiation of large cells into immunoglobulin secreting cells. Second, a specific interaction between C1q and laminin, a major macromolecular component of basement membranes, was demonstrated suggesting a possible role for C1q in the deposition of immune complexes in basement membranes. Third, we are continuing an investigation of cells which synthesize C1q, specifically fibroblasts and in vitro differentiating monocytes, to ascertain the availability of functionally active C1q at extravascular sites.